Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP- Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP- Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-κB activation. It is noteworthy that CLP- Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprusside, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction, Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.

Transmission of urothelial carcinoma via solid organ transplant has never been reported in the literature to our knowledge. We report a case of transmission of this tumour to a kidney recipient. The donor was a 37-year-old woman, victim of a subarachnoid haemorrhage. The recipient was a 21-year-old girl, with a history of chronic kidney disease secondary to neurogenic bladder. This fatality has been rarely described in literature, but never with this histological type of cancer. Nowadays, with the expanded criteria for donation, older people are accepted as donor because of the shortage of organs. However, this may increase the likelihood of the number of cancer transmission.

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Renal expression of CD68 and the chronicity index are associated with progression to chronic kidney disease in patients with proliferative LN.

Introduction IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide. According to the Oxford Classification, changes in the kidney vascular compartment are not related with worse outcomes. This paper aims to assess the impact of thrombotic microangiopathy (TMA) in the outcomes of Brazilian patients with IgAN. Materials and methods Analysis of clinical data and kidney biopsy findings from patients with IgAN to assess the impact of TMA on renal outcomes. Results The majority of the 118 patients included were females (54.3%); mean age of 33 years (25;43); hypertension and hematuria were observed in 67.8% and 89.8%, respectively. Median creatinine: 1.45mg/dL; eGFR: 48.8ml/min/1.73m 2 ; 24-hour proteinuria: 2.01g; low serum C3: 12.5%. Regarding to Oxford Classification: M1: 76.3%; E1: 35.6%; S1: 70.3%; T1/T2: 38.3%; C1/C2: 28.8%. Average follow-up: 65 months. Histologic evidence of TMA were detected in 21 (17.8%) patients and those ones presented more frequently hypertension (100% vs . 61%, p <0.0001), hematuria (100% vs 87.6%, p = 0.0001), worse creatinine levels (3.8 vs . 1.38 mg/dL, p = 0.0001), eGFR (18 vs . 60 ml/min/1.73m 2 ), p = 0.0001), low serum C3 (28.5% vs . 10.4%, p = 0.003), lower hemoglobin levels (10.6 vs . 12.7g/dL, p< 0.001) and platelet counts (207,000 vs . 267,000, p = 0.001). Biopsy findings of individuals with TMA revealed only greater proportions of E1 (68% vs . 32%, p = 0.002). Individuals with TMA were followed for less time (7 vs . 65 months, p<0.0001) since they progressed more frequently to chronic kidney disease (CKD) requiring kidney replacement therapy (KRT) (71.4% vs . 21,6%, p<0.0001). Male sex, T1/T2, and TMA were independently associated with progression to CKD-KRT. Conclusions In this study patients with TMA had worse clinical manifestations and outcomes. In terms of histologic evidence, E1 distinguished patients with TMA from other patients. Further studies are necessary to analyze the impact of vascular lesions on IgAN prognosis.

The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine- kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.